Study of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer

NCT05065957 | Recruiting Phase 2 FDA Drug

• 1 other identifier: Inno-GO-05
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective are: To assess the safety and tolerability of the combination of D07001-softgel capsules and Xeloda/TS-1. To evaluate the efficacy of the combination of D07001-softgel capsules and Xeloda/TS-1, as assessed by disease control rate (DCR).

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)/ serious adverse event (SAEs)

  AEs will be assessed via the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  From date of informed consent to 30-day follow-up visit for each subject

• To assess disease control rate (DCR)

  To assess DCR, the percentage of treatment patients who achieved CR, PR, or SD.

  From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months

Secondary Outcomes (5)

• Phase IIa and IIb: Pharmacokinetics (PK) of gemcitabine (dFdC), difluorodeoxyuridine (dFdU), capecitabine, 5-FU, Tegafur, Gimeracil, and Oteracil potassium

  Cycle 1 Days 1, 8, and 12 (each cycle is 21 days)

• Quality of life (QOL) will be assessed using the EORTC questionnaires

  Cycle 1 Days 1, and date of withdraw the study (assessed up to 24 months) for each subject (each cycle is 21 days)

• To assess Progression-free survival (PFS)

  From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months

• To assess Objective response rate (ORR)

  From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months

• To assess overall survival (OS)

  The survival follow-ups will follow every 6 weeks from date of discontinued study drug for up to 24 months till the death of the subject or closure of the study.

Study Arms (2)

Phase IIa:Dose-Finding Stage

EXPERIMENTAL

Level -5: 20 mg D07001-softgel capsules plus 625 mg/m\^2 Xeloda (or 20/30/40 mg TS-1). Level -4: 40 mg D07001-softgel capsules plus 625 mg/m\^2 Xeloda (or 20/30/40 mg TS-1). Level -3: 60 mg D07001-softgel capsules plus 625 mg/m\^2 Xeloda (or 20/30/40 mg TS-1). Level -2: 80 mg D07001-softgel capsules plus 625 mg/m\^2 Xeloda (or 20/30/40 mg TS-1). Level -1 (starting dose): 100 mg D07001-softgel capsules plus 625 mg/m\^2 Xeloda (or 20/30/40 mg TS-1). Level 1: 100 mg D07001-softgel capsules plus 800 mg/m\^2 Xeloda (or 30/40/50 mg TS-1). Level 2: 100 mg D07001-softgel capsules plus 1000 mg/m\^2 Xeloda (or 40/50/60 mg TS-1).

Drug: D07001-softgel capsules + Xeloda (or TS-1)

Phase IIb/III: Dose Expansion Stage

ACTIVE COMPARATOR

ASC+ D07001-softgel capsules plus Xeloda (or TS-1) ASC+mFOLFOX (5-FU+Oxalipatin+folinic acid)

Drug: D07001-softgel capsules + Xeloda (or TS-1); Drug: mFOLFOX

Interventions

D07001-softgel capsules + Xeloda (or TS-1) DRUG

D07001-softgel capsules: 3 times per week (on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle, 9 doses per cycle). Xeloda (or TS-1): twice daily for 14 consecutive days followed by 7 days rest (1 treatment cycle)

Also known as: Treatment group

Phase IIa:Dose-Finding Stage; Phase IIb/III: Dose Expansion Stage

mFOLFOX DRUG

intravenous infusion on Day 1 for 14-day cycle

Also known as: Control group

Phase IIb/III: Dose Expansion Stage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years or older at screening (aged 20 years or older in Taiwan)
• Histopathological or cytologic diagnosis of unresectable metastatic or locally advanced BTC (cholangiocarcinoma, gallbladder cancer or ampullary carcinoma)
• Subject must have failed from first line gemcitabine and cisplatin-based chemotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• Life expectancy is \>12 weeks
• Adequate bone marrow function, demonstrated by:
• Absolute neutrophil count (ANC) ≥1,500 cell/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin ≥ 9 g/dL
• Adequate liver function, demonstrated by:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or ≤5.0 x ULN in the case of liver metastases
• Total bilirubin ≤1.5 x ULN
• Albumin ≥3.0 g/dL
• International normalized ratio (INR) \<1.5
• Adequate renal function, demonstrated by:

You may not qualify if:

• Have prior chemotherapy regimen other than first line gemcitabine and cisplatin-based therapy for unresectable metastatic or locally advanced BTC Note: prior fluoropyrimidine base (including capecitabine, carmofur (HCFU), doxifluridine, fluorouracil (5-FU), and tegafur) chemotherapy (including fluoropyrimidine monotherapy or combination therapy) are allowed as postsurgical adjuvant therapy.
• Diagnosis of active malignancy other than BTC within the past 2 years, except nonmelanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent
• Prior discontinuation of gemcitabine because of pulmonary or hepatic toxicity or hemolytic uremic syndrome (HUS) or hypersensitivity, allergic reaction, or intolerance
• Known or suspected hypersensitivity to capecitabine, tegafur, gimeracil, oteracil potassium, oxaliplatin or other platinum compounds, leucovorin products, folic acid or folinic acid, 5-fluorouracil or their excipients.
• Prior discontinuation of fluoropyrimidine because of any unexpected or severe reaction.
• Treatment with brivudine, sorivudine, or its chemically-related analogs ≤ 28 days prior to the date of enrollment.
• Under flucytosine treatment.
• Residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2 neuropathy and alopecia are permitted)
• Any GI disorder which would significantly impede absorption of an oral agent
• Known brain or leptomeningeal metastases
• Major surgery or definitive ablation-intent (excluding palliative radiotherapy for bone metastasis) radiation therapy within the past 28 days
• Any active disease or condition that would not permit compliance with the protocol
• Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, congestive heart failure, or New York Heart Association \[NYHA\] Grade 2 or greater), or uncontrolled serious cardiac arrhythmia
• Have documented cerebrovascular disease. Subjects with the disease may be excluded, but if the investigator assesses that they are asymptomatic or well controlled could be enrolled.
• Have a seizure disorder not controlled on medication (based on decision of Investigator)

Sponsors & Collaborators

• InnoPharmax Inc.: lead

Study Sites (5)

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

RECRUITING

China Medical University Hospital

Taichung, 404, Taiwan

RECRUITING

National Taiwan University Cancer Center

Taipei, Taiwan

RECRUITING

National Taiwan University Hospotal

Taipei, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Capecitabine; titanium silicide; Control Groups

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Li-Tzong Chen, Ph.D

  National Institute of Cancer Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuyuan Lin

CONTACT

886-87977607; yuan.lin@innopharmax.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In phase IIa, a modified 3+3 dose-finding design trial will be conducted to identify the selected dose of the combination of D07001-softgel capsules plus Xeloda (or TS-1). After the dose-finding stage will be completed, a phase IIb/III adaptive design, open label, multicenter, active controlled, parallel-group trial will be implemented and incorporated into a dose-expansion stage to evaluate the efficacy and safety of D07001-softgel capsules plus Xeloda.

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: October 4, 2021
• Study Start: March 29, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 30, 2025

Record last verified: 2025-04

Locations

TW (5)